Exploiting the chikungunya virus capsid protein: a focused target for antiviral therapeutic development

Chikungunya disease is spread by the bite of infected Aedes mosquitoes. It is considered a neglected tropical disease that has the potential to cause sporadic epidemics in naive populations. Despite the substantial investment in research, there are no approved antiviral treatments for chikungunya. Several screening approaches have been used to identify potential antiviral molecules that target the whole virus, viral proteins, and viral-host interactions, often in conjunction with computational studies. The genome of chikungunya virus (CHIKV) encodes four nonstructural and five structural proteins. The capsid protein (CP) is a small structural protein with enzymatic activity. Owing to its critical role in different stages of the viral life cycle, the CP can be targeted at multiple stages, thereby impeding viral multiplication. There is evidence suggesting that the CP may be a promising target for drug development, and this has led to the discovery of various inhibitors through diverse in vitro and in silico analyses. Both cell-based and cell-free assays have been widely used to identify and evaluate CHIKV CP inhibitors. Computer-based studies targeting CHIKV proteins, including CP, have identified several lead compounds, which are being further evaluated in various in vitro systems. No review has been published on the CHIKV CP, and papers have focused on drug development and the targeting of viral proteins and associated factors. In this review, we summarize the research that has been conducted on the CHIKV CP, including structural studies, antiviral research, and prospects for the use of the CP as an antiviral target.